Unlock instant, AI-driven research and patent intelligence for your innovation.

Chemoenzymatic methods for synthesizing moenomycin analogs

a moenomycin analog and moenomycin technology, applied in the direction of esterified saccharide compounds, sugar derivates, transferases, etc., can solve the problems of high serum binding, poor pharmacokinetic properties of moenocinol chains, and high resistance to existing antibiotics

Active Publication Date: 2018-02-27
PRESIDENT & FELLOWS OF HARVARD COLLEGE
View PDF98 Cites 0 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Benefits of technology

The patent describes how to make a compound called moenomycin A, which is a potent inhibitor of a bacterial enzyme. The invention provides methods for making this compound using a specific enzyme called GalT. The invention also provides kits and compositions containing GalT. This technology can be used to develop new antibiotics that target specific enzymes in bacteria.

Problems solved by technology

Over the past 10 years, resistance to existing antibiotics has become a significant problem in many countries.
The major hurdle in designing such drugs is that in addition to enzyme based activity these drugs need to cross the bacterial cell wall to exert their antibacterial effect.
However, at the same time, the moenocinol chain is also credited with poor pharmacokinetic properties and high serum binding of meonomycin, e.g., its absorption upon oral administration is relatively poor.

Method used

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
View more

Image

Smart Image Click on the blue labels to locate them in the text.
Viewing Examples
Smart Image
  • Chemoenzymatic methods for synthesizing moenomycin analogs
  • Chemoenzymatic methods for synthesizing moenomycin analogs
  • Chemoenzymatic methods for synthesizing moenomycin analogs

Examples

Experimental program
Comparison scheme
Effect test

examples

Chemical Syntheses

[0293]All reactions in non-aqueous reaction medium were carried out under an atmosphere of argon, unless otherwise noted. Commercial chemicals were used without prior purification. Solvents were dried by passage over columns filled with activated aluminum oxide (Glass Contour Solvent Systems, SG Water USA, Nashua, N.H., USA).

[0294]

Synthesis of S2 and S3

General procedure for preparation of 2,5-Di-O-alkyl-D-Mannitol

[0295]To a stirred suspension of 60% NaH (3 equiv.), washed twice with petroleum ether, in anhydrous DMF (8 mL / mmol-starting material (SM)) was added 1,3:4,6-di-O,O-(4-methoxybenzylidene)-D-mannitol (1 equiv., SM) at room temperature. After being stirred for 30 min, the mixture was treated with a 1.2 M solution of alkylating reagents (2.4 equiv., Br, and methane- or p-toluene-sulfonate for R=allyl, and n-alkyl groups, respectively) in anhydrous DMF and a catalytic amount of tetrabutylammonium iodide for allyl-Br, or 15-Crown-5 for n-alkyl sulfonates. The r...

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
Login to View More

PUM

PropertyMeasurementUnit
Rgaaaaaaaaaa
temperatureaaaaaaaaaa
temperatureaaaaaaaaaa
Login to View More

Abstract

The present invention provides methods of synthesizing moenomycin analogs of Formula (I). The present invention also provides compositions comprising a compound of Formula (I) and kits for synthesizing compounds of Formula (I).

Description

RELATED APPLICATIONS[0001]The present application is a national stage filing under 35 U.S.C. § 371 of international PCT application, PCT / US2013 / 035427, filed Apr. 5, 2013, which claims priority under 35 U.S.C. § 119(e) to U.S. provisional patent application, U.S. Ser. No. 61 / 621,186, filed Apr. 6, 2012, each of which is incorporated herein by reference.GOVERNMENT FUNDING[0002]This invention was made with U.S. Government support under GM066174, GM076710, and AI083214 awarded by National Institutes of Health. The U.S. Government has certain rights in the invention.BACKGROUND OF THE INVENTION[0003]Bacteria have the ability to generate resistance to antibiotics through lateral gene transfer, mutation of enzymes, or the expression of enzymes which actively pump the antibiotic out of the cell or break it down. Over the past 10 years, resistance to existing antibiotics has become a significant problem in many countries. Vancomycin is currently the drug of last resort to combat multidrug-re...

Claims

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
Login to View More

Application Information

Patent Timeline
no application Login to View More
Patent Type & Authority Patents(United States)
IPC IPC(8): C12P19/44C07H1/00C07H13/00C07H13/04C12P19/18C12N9/12
CPCC12P19/44C07H1/00C07H13/00C12N9/1241C12P19/18C07H13/04C12Y207/07012
Inventor KAHNE, DANIEL EVANKAHNE, SUZANNE WALKERDOUD, EMMAGAMPE, CHRISTIAN M.TSUKAMOTO, HIROKAZU
Owner PRESIDENT & FELLOWS OF HARVARD COLLEGE